SEEDED: Deep Sequencing Analysis in Personalized Medicine

SEEDED Summer School 2017 combined presentations of invited speakers with discussions, practical experimental work and data analysis. It covered the complete work-flow for the analysis of epigenetic deregulation with complementary “multi-readout” data sets.

In three modules a structured training program has been set up on epigenetic deregulation, which can be used for patient stratification and prediction of drug response. Module 1 – an interactive lecture workshop  – provided the general framework for studying disease related epigenetic deregulation using Deep Sequencing methods.  Module 2 and 3 - hands-on workshops – explained the experimental process and bioinformatic analysis of data.
The e:Med SEEDED Summer School 2017 mainly focused on Epigenetics in Systems Medicine and was aimed to strengthen methodological skills of young scientists and to open up new ways of viewing their own projects. In order to approach this systems medicine topic interdisciplinarily, 14 selected participants and 14 speakers met in Heidelberg. Their areas of research ranged from cancer to malaria up to obesity and diabetes.

Key topic: Epigenetic Deregulation in the context of diseases

Disease therapy is facing a fundamental paradigm shift towards individualized therapy. To implement such an approach, a thorough personalized molecular characterization of the patient is essential. Towards this goal genome-wide sequencing methods currently find their way into clinics. In addition to the sole decoding of the DNA sequence, the epigenome and the transcriptome of the cell convey a lot of information about a person’s medical condition and can be used as biomarkers. A personalized, epigenetic readout of a person’s disease state is ideally suited to guide clinical decision making.
During the SEEDED Summer School young scientists were able to experience how epigenetic data from a limited amount of patient samples can be analyzed and integrated.
In the first part of the Summer School – the interactive lecture workshop at the Crowne Plaza, Heidelberg –methodological approaches as well as data management were given a closer look with regard to epigenetic deregulation in systems medicine. This was followed up by topics regarding mechanisms of epigenetic regulation and issues particularly concerning sample preparation, project planning, standardization and validation.

Right at the beginning the importance of methodological knowledge was demonstrated in exciting presentations, in order to use Big Data in medical research to help improve diagnosis, stratification and new therapy approaches. Quite impressively case studies were shown, in which epigenetic therapies have a very promising outcome, for example, the treatment of pediatric tumors. Experiences with major sequencing projects like ICGC, DEEP /IHEC, INFORM or HIPO-DKFZ have also been reported.
“Break out sessions”, in which participants and lecturers intensively discussed their issues in small groups, where embedded in the lecture program. As an example, regarding the heterogeneity of diseases, it was discussed, which important criteria can be obtained by sequencing the epigenome and transcriptome.

The Chromatin networks and epigenetic regulation session triggered especially intense discussion – in this lecture, topics from implementation of epigenomic interpretations to simulation models concerning “transcription factories” up to quantitative data analysis (e.g. differences in the DNA methylation) have been on the agenda.
Examples for poor study design and their consequences in order to draw attention to potential pitfalls and challenges were also outlined to the participants.
Overall, the wide range of topics and diverse aspects of epigenetic deregulation at the SEEDED Summer School were assessed very positively by the participants. The presentations were rich in content and well-coordinated with one another. The intensive discussion among the interdisciplinary group of participants and speakers throughout the entire lecture workshop, during the breaks and also at the evening event, were especially emphasized. Thus participants had plenty of time and opportunities to discuss their issues with the speakers.

Experimental analysis of the functional epigenome at EMBL

The hands-on course to generate high-resolution sequencing data, serves as the experimental foundation for the integrative analysis of epigenetic data, due in September. The process had been optimized for the use of limited amounts of primary cells.
The participants had the opportunity to try it out themselves and test analyzing three integrated deep sequencing data sets.
To evaluate the interaction between epigenetic signals, accessibility of chromatin and transcriptome, various methods were applied and different data sets were created: genome-wide bisulfite sequencing (WGBS), ATAC-seq and RNA-seq. This data enables to evaluate epigenetic signaling pathways (WGBS), active and accessible enhancer and promoter sequences (ATAC-seq), as well as functional effects on gene expression (RNA-seq).

During incubation times the instructors repeatedly gave brief overviews on troubleshooting and tips and tricks on how to handle samples. Technical challenges, troubleshooting and possible pitfalls were treated as well as the necessary adaptation of protocols to ensure an efficient use of technology with different materials. The hands-on workshop was accompanied by poster sessions, in which the participants also had the opportunity to ask specific questions regarding their project and intensively exchanged ideas and information.
The experimental work has been described as enormously helpful and valuable by the participants. Especially troubleshooting and problem-handling concerning their own projects have been appreciated a lot. Particularly pointed out were the excellent preparation and the highly motivated and competent team.

 

Excursions to the Philosopher's Walk and Neckar River Valley -including a boat trip and castle visiting - stimulated further exchange of ideas among the scientists in a relaxed atmosphere and rounded off the July workshop nicely.

Module three will concentrate on practical bioinformatic analysis of the generated sequencing data.
The workshop will be held in September by the Heidelberg Center for Human Bioinformatics (HD-HuB) within the de.NBI-Program.